Malaria control is seriously limited in Africa by the increasing resistance of parasites to available drugs. Important needs are the characterization of drug resistance and the assessment of the comparative efficacy of available drugs. These goals require skilled personnel and a complex infrastructure for research. This proposal describes a training program for Uganda that builds on a collaboration between UCSF and Makerere University that began in 1998, has engaged Ugandan and American trainees, and has established a productive center for clinical malaria research in Kampala. The principal goal of this project will be to train Ugandans in modem methods of clinical, epidemiological, and molecular research. A secondary goal will be to establish the necessary infrastructure for the performance of modern mlecular research in Uganda. These are broad objectives, but they will be pursued in a focused manner, with all research activities directed toward the evaluation of antimalarial drug efficacy and resistance in Kampala. For all activities, trainees will receive one-on-one mentoring from project faculty and appropriate coursework. In some cases, activities may lead to degree-granting programs in epidemiology or biochemistry. Specific aims of the project will be as follows. a. Training Ugandan Investigators in clinical malaria research. Trainees will participate in ongoing projects in Kampala assessing and comparing the antimalarial efficacy of available and experimental drugs. b. Training Ugandan investigators in epidemiologic methods relevant to the study of antimalarial drug resistance. Trainees will link core studies at either Makerere University or the University of California (UCSF and UC Berkeley) with evaluations of the epidemiology of antimalarial drug resistance in kampala. c. Training Ugandan investigators in methods of molecular parasitology research pertinent to the study of antimalarial drug resistance. Trainees will take part in laboratory research activities at molecular parasitology laboratories at Makerere University and at UCSF that are directed toward the elucidation of mechanisms of antimalarial drug resistance and are appropriate for the developing country setting.